Brain-Enhancing Chemicals

Uncovering this information earned Arvid Carlsson, Paul Greengard and Eric Kandel the Physiology or Medicine Prize in 2000. Through their pioneering studies, the three scientists showed how neurotransmitters influence basic functions of the brain and how they are affected by disease.

Carlsson's research into neurotransmitters revealed, for the first time, how a brain disorder actually worked. After discovering a transmitter called dopamine, he found that reducing levels of it in the brains of experimental animals created symptoms like Parkinson's disease, a so-called neurodegenerative disease that causes severe movement problems. From this Carlsson deduced that the disease is caused by a loss of dopamine in brain regions affecting control of movements, and that it should be possible to treat with the dopamine boosting drug L-DOPA, which has brought relief to millions of Parkinson's sufferers.

Greengard showed how dopamine and other neurotransmitters trigger these types of effects in nerve cells. His studies built directly on the work of Earl Sutherland and Ed Krebs, who found in the 1960s that there are two types of receptor for neurotransmitters. When a transmitter locks onto and opens a ligand-gate (also known as an 'ionotropic receptor'), it sparks out a synaptic potential instantly, and it's all over in milliseconds. Sutherland and Krebs discovered another kind of receptor, called a metabotropic receptor, which produces a very different response that is much more widespread and can go on for minutes.

Greengard painstakingly assembled a complete picture of the events that occur during these 'slow' synaptic signals. When dopamine locks on to a metabotropic receptor, it releases a so-called 'second messenger' inside the cell called cyclic AMP, which activates protein kinase A, a kind of master switch that can activate a host of biologically important proteins by adding phosphate molecules onto them. Greengard identified over one hundred of these activated chemicals, and found how they interact in elaborate cascades to alter the way the cell behaves and reacts. These discoveries are helping to build a detailed picture of how the neuron's biochemical software works.

How neurotransmitters work part 2.

When dopamine and other neurotransmitters reach the receiving nerve cell they attach themselves to two types of receptors. One type of receptor sparks off a nerve impulse within milliseconds. Another type triggers a slower event, where messenger molecules set off an elaborate chain of chemical events, which eventually activates a host of biologically important proteins that alter the way the nerve cell behaves and reacts.
Copyright: The Nobel Committee for Physiology or Medicine at Karolinska Institutet.

Meanwhile, Kandel was showing just what it was all programmed to do - store memories. Kandel pioneered the idea that nerves remember things because of changes at synapses, and that learning is all about activating second-messenger cascades of the type studied by Greengard. Remembering things means, essentially, unleashing the right cascades of chemicals to reinforce the connections between neurons along particular pathways.


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